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Background: Colon cancer occurrence is increasing worldwide, making it the third most frequent cancer. Although many therapeutic options are available and quite efficient at the early stages, survival is strongly decreased when the disease has spread to other organs. The identification of molecular markers of colon cancer is likely to help understanding its course and, eventually, to uncover novel genes to be targeted by drugs. In this study, we compared gene expression in a set of 95 human colon cancer samples to that in 19 normal colon mucosae, focusing on 401 genes from 5 selected pathways (Apoptosis, Cancer, Cholesterol metabolism and lipoprotein signaling, Drug metabolism, Wnt/beta-catenin). Deregulation of mRNA levels largely matched that of proteins, leading us to build in silico protein networks, starting from mRNA levels, to identify key proteins central to network activity. Results: Among the analyzed genes, 10.5% (42) had no reported link with colon cancer, including the SFRP1, IGF1 and ADH1B (down), and MYC and IL8 (up), whose encoded proteins were most interacting with other proteins from the same or even distinct networks. Analyzing all pathways globally led us to uncover novel functional links between a priori unrelated or rather remotely connected pathways, such as the Drug metabolism and the Cancer pathways or, even more strikingly, between the Cholesterol metabolism and lipoprotein signaling and the Cancer pathways. In addition, we analyzed the responsiveness of some of the deregulated genes essential to network activities, to chemotherapeutic agents used alone or in presence of Lovastatin, a lipid-lowering drug. Some of these treatments could oppose the deregulations occurring in cancer samples, including those of the CHECK2, CYP51A1, HMGCS1, ITGA2, NME1 or VEGFA genes. Conclusions: Our network-based approach allowed discovering genes not previously known to play regulatory roles in colon cancer. Our results also showed that selected drug treatments might revert the cancer-specific deregulation of genes playing prominent roles within the networks operating to maintain colon homeostasis. Among those genes, some could constitute novel testable targets to eliminate colon cancer cells, either directly or, potentially, through the use of lipid-lowering drugs such as statins, in association with selected anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Interferon induced transmembrane proteins 1, 2 and 3 (IFITMs) belong to a family of highly related antiviral factors that have been shown to interfere with a large spectrum of viruses including Filoviruses, Coronaviruses, Influenza virus, Dengue virus and HIV-1. In all these cases, the reported mechanism of antiviral inhibition indicates that the pool of IFITM proteins present in target cells blocks incoming viral particles in endosomal vesicles where they are subsequently degraded. Results: In this study, we describe an additional mechanism through which IFITMs block HIV-1. In virus-producing cells, IFITMs coalesce with forming virions and are incorporated into viral particles. Expression of IFITMs during virion assembly leads to the production of virion particles of decreased infectivity that are mostly affected during entry in target cells. This mechanism of inhibition is exerted against different retroviruses and does not seem to be dependent on the type of Envelope present on retroviral particles. Conclusions: The results described here identify a novel mechanism through which IFITMs affect HIV-1 infectivity during the late phases of the viral life cycle. Put in the context of data obtained by other laboratories, these results indicate that IFITMs can target HIV at two distinct moments of its life cycle, in target cells as well as in virus-producing cells. These results raise the possibility that IFITMs could similarly affect distinct steps of the life cycle of a number of other viruses. [ABSTRACT FROM AUTHOR]

Background: The bovine spongiform encephalopathy (BSE) epidemic presented homogeneity of the phenotype. This classical BSE (called C-type) was probably due to the contamination of the food chain by a single prion strain. However, due to the active surveillance and better techniques, two rare variants of BSE have been recently reported in different continents without a clear correlation to the BSE epidemic. These emerging types behave as different strains of BSE and were named H-type and L-type according to the high and low molecular mass of the unglycosylated fragment of their proteinase K resistant prion protein (PrPres). In these types, the proportion of the un-, mono- and di-glycosylated fragments of PrP (glycoprofile) is also atypical and represents an effective diagnostic parameter. This study evaluated the presence of such types in bovine of 7 years and older in Belgium. Results: The Belgian BSE archive contained 41 bovines of at least 7 years of age. The biochemical features of their PrPres were analyzed by Western blot with five antibodies recognising different regions of PrPres, from N- to C-terminus: 12B2, 9A2, Sha31, SAF84 and 94B4. All antibodies clearly detected PrPres except 12B2 antibody, which is specific for N-terminal region 101-105, a PrP region that is only retained in H-types. The glycoprofiles did correspond to that of C-type (with more than 55% of diglycosylated PrPres using antibody 94B4). Therefore, all cases have the features of C-type BSE. Conclusions: This study supports that, among the BSE cases of 7 years and older identified in Belgium, none was apparently of the H- or L- type. This is consistent with the very rare occurrence of atypical BSE and the restricted dimension of Belgium. These results shed some light on the worldwide prevalence of atypical BSE. [ABSTRACT FROM AUTHOR]